title: Live attenuated Rev-independent Nef¯SIV enhances acquisition of heterologous SIVsmE660 in acutely vaccinated rhesus macaques.
abstract: BACKGROUND
  Rhesus macaques (RMs) inoculated with live-attenuated Rev-Independent Nef¯ simian immunodeficiency virus (Rev-Ind Nef¯SIV) as adults or neonates controlled viremia to undetectable levels and showed no signs of immunodeficiency over 6-8 years of follow-up. We tested the capacity of this live-attenuated virus to protect RMs against pathogenic, heterologous SIVsmE660 challenges.
  
  
  RESULTS
  Three groups of four RM were inoculated with Rev-Ind Nef¯SIV and compared. Group 1 was inoculated 8 years prior and again 15 months before low dose intrarectal challenges with SIVsmE660. Group 2 animals were inoculated with Rev-Ind Nef¯SIV at 15 months and Group 3 at 2 weeks prior to the SIVsmE660 challenges, respectively. Group 4 served as unvaccinated controls. All RMs underwent repeated weekly low-dose intrarectal challenges with SIVsmE660. Surprisingly, all RMs with acute live-attenuated virus infection (Group 3) became superinfected with the challenge virus, in contrast to the two other vaccine groups (Groups 1 and 2) (P=0.006 for each) and controls (Group 4) (P=0.022). Gene expression analysis showed significant upregulation of innate immune response-related chemokines and their receptors, most notably CCR5 in Group 3 animals during acute infection with Rev-Ind Nef¯SIV.
  
  
  CONCLUSIONS
  We conclude that although Rev-Ind Nef¯SIV remained apathogenic, acute replication of the vaccine strain was not protective but associated with increased acquisition of heterologous mucosal SIVsmE660 challenges.
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America ; Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Siddappa N
authors.initials: SN
authors.lastname: Byrareddy
authors.forename: Mila
authors.initials: M
authors.lastname: Ayash-Rashkovsky
authors.forename: Victor G
authors.initials: VG
authors.lastname: Kramer
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Mick
authors.initials: M
authors.lastname: Correll
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Novembre
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: Welkin E
authors.initials: WE
authors.lastname: Johnson
authors.forename: Agneta
authors.initials: A
authors.lastname: von Gegerfelt
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Felber
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Ruprecht
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D015694:Gene Products, rev / Q000235:genetics; D007113:Immunity, Innate / Q000276:immunology*; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus; D016896:Treatment Outcome; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics; D014766:Viremia / Q000276:immunology*
chemical_list: D015694:Gene Products, rev; C429284:NEF protein, SIV; D014613:Vaccines, Attenuated; D054334:Viral Regulatory and Accessory Proteins